tbuckley/cabot-search huggingface dataset:
Association of Birth Weight Centiles and Gestational Age With Cognitive Performance at Age 5 Years
Authors: Robert Eves, Dieter Wolke, Juliane Spiegler, Sakari Lemola
Journal: JAMA Network Open (2023)

Birth weight percentiles (BWPs) are often dichotomized at the 10th percentile and show statistically significant association with later cognitive performance, for both preterm and term-born children. However, research testing nonlinear associations between BWPs and cognitive performance is scarce.To investigate culturally invariant, nonlinear associations of BWPs and gestational age with later cognitive performance.In this cohort study, participants with valid neonatal and cognitive data were combined from 4 observational cohorts, including the Millennium Cohort Study, the National Longitudinal Survey of Youth 1979 Child and Young Adult cohort, Growing Up in Ireland, and the Longitudinal Study of Australian Children, with children born between 2000 and 2002, 1980 and 2010, 2007 and 2008, and 2003 and 2004, respectively. Neonatal data were parent reported before age 1 year. At approximately 5 years of age, multiple cognitive tests were performed. Follow-up at 5 years of age was the predominant focus. Data were analyzed July 17, 2023.The parent-reported neonatal data were used to calculate BWPs according to the Fenton growth chart.Scores for IQ were created from multiple measures of cognition, which were z standardized separately within each cohort.Of 30 643 participants (50.8% male), 7.5% were born preterm (before 37 weeks gestation) and 92.5% were term born (between 37 and 42 weeks gestation). In the pooled data using multivariate adaptive regression splines, IQ linearly increased by 4.2 points as BWPs increased from the first to the 69th percentile before completely plateauing. For gestational age, IQ linearly increased by 1.3 points per week up until 32 weeks, with the association reducing to 0.3 points per week after 32 weeks. The association of BWP with IQ was not moderated by gestational age. For term-born infants, the estimated IQ score was only clinically meaningfully lower than average when birth weight was below the third percentile. Consistent results were found when instead using multivariable regression where gestational age and BWPs were categorized into groups.In this cohort study, lower BWPs and gestational age were independently associated with lower IQ. For term-born infants, a cutoff of the third percentile would be more appropriate than the traditionally used 10th percentile when the aim is estimating meaningful cognitive differences.
Thermostable allergens in canned fish: Evaluating risks for fish allergy
Authors: Aya C. Taki, Thimo Ruethers, Roni Nugraha, Shaymaviswanathan Karnaneedi, Nicholas A. Williamson, Shuai Nie, Michael G. Leeming, Sam S. Mehr, Dianne E. Campbell, Andreas L. Lopata
Journal: Allergy (2023)

Abstract Background Major fish allergens, including parvalbumin (PV), are heat stable and can withstand extensive cooking processes. Thus, the management of fish allergy generally relies on complete avoidance. Fish‐allergic patients may be advised to consume canned fish, as some fish‐allergic individuals have reported tolerance to canned fish. However, the safety of consuming canned fish has not been evaluated with comprehensive immunological and molecular analysis of canned fish products. Methods We characterized the in vitro immunoreactivity of serum obtained from fish‐allergic subjects to canned fish. Seventeen canned fish products (salmon n = 8; tuna n = 7; sardine n = 2) were assessed for the content and integrity of PV using allergen‐specific antibodies. Subsequently, the sIgE binding of five selected products was evaluated for individual fish‐allergic patients ( n = 53). Finally, sIgE‐binding proteins were identified by mass spectrometry. Results The canned fish showed a markedly reduced PV content and binding to PV‐specific antibodies compared with conventionally cooked fish. However, PV and other heat‐stable fish allergens, including tropomyosin and collagen, still maintained their sIgE‐binding capacity. Of 53 patients, 66% showed sIgE binding to canned fish proteins. The canned sardine contained proteins bound to sIgE from 51% of patients, followed by canned salmon (43%–45%) and tuna (8%–17%). PV was the major allergen in canned salmon and sardine. Tropomyosin and/or collagen also showed sIgE binding. Conclusion We showed that canned fish products may not be safe for all fish‐allergic patients. Canned fish products should only be considered into the diet of individuals with fish allergy, after detailed evaluation which may include in vitro diagnostics to various heat‐stable fish allergens and food challenge conducted in suitable environments.
Ongoing measles outbreaks in Romania, March 2023 to August 2023
Authors: Mihaela Lazar, Cătălina Pascu, Maria Roșca, Aurora Stănescu
Journal: Eurosurveillance (2023)

Measles cases have recently been increasing in Romania, with 460 confirmed cases by August 2023. From March 2023, measles cases increased, and outbreaks were recorded in Cluj, Bistrita Nasaud, Sibiu and Mures counties. New D8 virus variants were identified, different from the variants detected in Romania before the COVID-19 pandemic. We here provide epidemiological and molecular data on the current increase in measles cases in the context of the measles elimination process in the World Health Organization European Region.
Mortality by Age, Gender, and Race and Ethnicity in People Experiencing Homelessness in Boston, Massachusetts
Authors: Danielle R. Fine, Kirsten A. Dickins, Logan D. Adams, Nora K. Horick, Natalia Critchley, Katherine Hart, Jessie M. Gaeta, Elizabeth Lewis, Sara E. Looby, Travis P. Baggett
Journal: JAMA Network Open (2023)

People experiencing homelessness (PEH) face disproportionately high mortality rates compared with the general population, but few studies have examined mortality in this population by age, gender, and race and ethnicity.To evaluate all-cause and cause-specific mortality in a large cohort of PEH by age, gender, and race and ethnicity.An observational cohort study was conducted from January 1, 2003, to December 31, 2018. All analyses were performed between March 16, 2021, and May 12, 2022. A cohort of adults (age ≥18 years) seen at the Boston Health Care for the Homeless Program (BHCHP), a large federally funded Health Care for the Homeless organization in Boston, Massachusetts, from January 1, 2003, to December 31, 2017, was linked to Massachusetts death occurrence files spanning January 1, 2003, to December 31, 2018.Age-, gender-, and race and ethnicity-stratified all-cause and cause-specific mortality rates were examined and compared with rates in the urban Northeast US population using mortality rate ratios (RRs).Among the 60 092 adults included in the cohort with a median follow-up of 8.6 (IQR, 5.1-12.5) years, 7130 deaths occurred. The mean (SD) age at death was 53.7 (13.1) years; 77.5% of decedents were men, 21.0% Black, 10.0% Hispanic/Latinx, and 61.5% White. The all-cause mortality rate was 1639.7 deaths per 100 000 person-years among men and 830 deaths per 100 000 person-years among women. The all-cause mortality rate was highest among White men aged 65 to 79 years (4245.4 deaths per 100 000 person-years). Drug overdose was a leading cause of death across age, gender, and race and ethnicity groups, while suicide uniquely affected young PEH and HIV infection and homicide uniquely affected Black and Hispanic/Latinx PEH.In this large cohort study of PEH, all-cause and cause-specific mortality varied by age, gender, and race and ethnicity. Tailored interventions focusing on those at elevated risk for certain causes of death are essential for reducing mortality disparities across homeless-experienced groups.
Solvent electrospinning amorphous solid dispersions with high itraconazole, celecoxib, mebendazole and fenofibrate drug loading and release potential
Authors: Jana Becelaere, Olmo Frateur, Ella Schoolaert, Valérie Vanhoorne, Dagmar R. D'hooge, Chris Vervaet, Richard Hoogenboom, Karen De Clerck
Journal: Journal of Controlled Release (2023)
Optimal Measurement of Coronary Flow and Microvascular Function in Animals and Humans
Authors: Lennert Minten, Michiel Algoet, Johan Bennett, Wouter Oosterlinck, Bart Meuris, Tom Langenaeken, Stephanie Bézy, Laurine Wouters, Jürgen Duchenne, Alexis Puvrez, Senne De Groote, Pierluigi Lesizza, Pascal Frederiks, Laurens De Vos, Tom Adriaenssens, Peter Sinnaeve, Walter Desmet, Keir McCutcheon, Christophe Dubois
Journal: Circulation Research (2023)

◼ microvascular angina ◼ reproducibility of results
Assessment of Prior Infection With Hepatitis B Virus and Fecundability in Couples Planning Pregnancy
Authors: Jun Zhao, Yan Xuan, Yue Zhang, Xiang Hong, Hongguang Zhang, Rong Zhang, Tao Yan, Yuanyuan Wang, Zuoqi Peng, Ya Zhang, Kailei Jiao, Tianyu He, Qiaomei Wang, Haiping Shen, Yiping Zhang, Donghai Yan, Bei Wang, Xu Ma
Journal: JAMA Network Open (2023)

The association of hepatitis B virus (HBV) infection with reduced fecundability among reproductive-aged couples lacks large-population, in-depth study evidence.To investigate the association of HBV infection with time to pregnancy in couples planning pregnancy, and to explore whether this association varied by gravidity, health statuses, or lifestyles.This is a population-based cohort study of Chinese couples participating in the National Free Preconception Check-up Projects during 2015 to 2017. They were planning pregnancy and were followed-up every 3 months until getting pregnant, as confirmed by gynecologic ultrasonography, or were followed-up for 1 year. Data were analyzed between March 1, 2022, and September 30, 2022.The main outcome was time to pregnancy, assessed using fecundability hazard ratios (HRs). The Cox proportional hazards regression models were used to estimate the association of HBV infection with fecundability.Among 2 419 848 couples (mean [SD] age, 27.87 [5.20] years for women and 29.58 [5.50] years for men), 126 728 women (5.24%) and 156 572 men (6.47%) were infected with HBV. Compared with the HBV-negative group, the fecundability of both women and men in the HBV-positive group decreased by 5% (HR, 0.95; 95% CI, 0.94-0.95). Compared with couples in which both partners were HBV negative, the fecundability of those in which both partners were HBV positive declined by 6% (HR, 0.94; 95% CI, 0.93-0.96) among all couples, by 3% (HR, 0.97; 95% CI, 0.95-0.99) among nulligravidas couples, and by 7% (HR, 0.93; 95% CI, 0.91-0.95) among multigravidas couples. Both the female-male and couple models suggested that the association of HBV infection with decreased fecundability was more pronounced in couples with multigravidas. The negative association was greater in people with overweight and obesity and was inconsistent in certain subgroups; in particular, it was more pronounced in women with reproductive tract infections, normal fasting plasma glucose, and no alcohol intake and in men with normal blood pressure.In this population-based cohort study, HBV infection was associated with decreased fecundability in a general reproductive-aged population, especially in couples with multigravidas. For women and men with certain health statuses and lifestyles, a comprehensive consideration of this association is recommended to provide personalized fertility guidance.
Single-Dose Psilocybin Treatment for Major Depressive Disorder
Authors: Charles L. Raison, Gerard Sanacora, Joshua Woolley, Keith Heinzerling, Boadie W. Dunlop, Randall T. Brown, Rishi Kakar, Michael Hassman, Rupal P. Trivedi, Reid Robison, Natalie Gukasyan, Sandeep M. Nayak, Xiaojue Hu, Kelley C. O’Donnell, Benjamin Kelmendi, Jordan Sloshower, Andrew D. Penn, Ellen Bradley, Daniel F. Kelly, Tanja Mletzko, Christopher R. Nicholas, Paul R. Hutson, Gary Tarpley, Malynn Utzinger, Kelsey Lenoch, Kasia Warchol, Theraysa Gapasin, Mike C. Davis, Courtney Nelson-Douthit, Steffanie Wilson, Carrie Brown, William Linton, Matthew W. Johnson, Stephen Ross, Roland R. Griffiths
Journal: JAMA (2023)

Psilocybin shows promise as a treatment for major depressive disorder (MDD).
Asymptomatic infection with clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) in carnivore pets, Italy, April 2023
Authors: Ana Moreno, Francesco Bonfante, Alessio Bortolami, Irene Cassaniti, Anna Caruana, Vincenzo Cottini, Danilo Cereda, Marco Farioli, Alice Fusaro, Antonio Lavazza, Pierdavide Lecchini, Davide Lelli, Andrea Maroni Ponti, Claudia Nassuato, Ambra Pastori, Francesca Rovida, Luigi Ruocco, Marco Sordilli, Fausto Baldanti, Calogero Terregino
Journal: Eurosurveillance (2023)

In April 2023, an outbreak of clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses carrying the T271A mammalian adaptive mutation in the PB2 protein was detected in a backyard poultry farm in Italy. Five domestic dogs and one cat living on the premises had seroconverted in the absence of clinical signs. Virological and serological monitoring of individuals exposed to the virus proved the absence of human transmission, however, asymptomatic influenza A(H5N1) infections in mammalian pets may have important public health implications.
Deaths Due to COVID-19 in Patients With Cancer During Different Waves of the Pandemic in the US
Authors: Alexandra L. Potter, Vedha Vaddaraju, Shivaek Venkateswaran, Arian Mansur, Simar S. Bajaj, Mathew V. Kiang, Anupam B. Jena, Chi-Fu Jeffrey Yang
Journal: JAMA Oncology (2023)

With the ongoing relaxation of guidelines to prevent COVID-19 transmission, particularly in hospital settings, medically vulnerable groups, such as patients with cancer, may experience a disparate burden of COVID-19 mortality compared with the general population.
Engineered short forms of perlecan enhance angiogenesis by potentiating growth factor signalling
Authors: Ha Na Kim, Zehra Elgundi, Xiaoting Lin, Lu Fu, Fengying Tang, Edward S.X. Moh, MoonSun Jung, Keerthana Chandrasekar, Florence Bartlett-Tomasetig, Candice Foster, Nicolle H. Packer, John M. Whitelock, Jelena Rnjak-Kovacina, Megan S. Lord
Journal: Journal of Controlled Release (2023)

Growth factors are key molecules involved in angiogenesis, a process critical for tissue repair and regeneration. Despite the potential of growth factor delivery to stimulate angiogenesis, limited clinical success has been achieved with this approach. Growth factors interact with the extracellular matrix (ECM), and particularly heparan sulphate (HS), to bind and potentiate their signalling. Here we show that engineered short forms of perlecan, the major HS proteoglycan of the vascular ECM, bind and signal angiogenic growth factors, including fibroblast growth factor 2 and vascular endothelial growth factor-A. We also show that engineered short forms of perlecan delivered in porous chitosan biomaterial scaffolds promote angiogenesis in a rat full thickness dermal wound model, with the fusion of perlecan domains I and V leading to superior vascularisation compared to native endothelial perlecan or chitosan scaffolds alone. Together, this study demonstrates the potential of engineered short forms of perlecan delivered in chitosan scaffolds as next generation angiogenic therapies which exert biological activity via the potentiation of growth factors.
Bone reconstruction of extensive maxillomandibular defects in adults
Authors: Peer W. Kämmerer, Bilal Al‐Nawas
Journal: Periodontology 2000 (2023)

Abstract Reconstruction of significant maxillomandibular defects is a challenge that has been much discussed over the last few decades. Fundamental principles were developed decades ago (bone bed viability, graft immobilization). Clinical decision‐making criteria are highly relevant, including local/systemic factors and incision designs, the choice of material, grafting technique, and donor site morbidity. Stabilizing particulated grafts for defined defects—that is, via meshes or shells—might allow significant horizontal and vertical augmentation; the alternatives are onlay and inlay techniques. More significant defects might require extra orally harvested autologous bone blocks. The anterior iliac crest is often used for nonvascularized augmentation, whereas more extensive defects often require microvascular reconstruction. In those cases, the free fibula flap has become the standard of care. The development of alternatives is still ongoing (i.e., alloplastic reconstruction, zygomatic implants, obturators, distraction osteogenesis). Especially for these complex procedures, three‐dimensional planning tools enable facilitated planning and a surgical workflow.
Sorafenib plus intensive chemotherapy in newly diagnosed <i>FLT3</i>-ITD AML: a randomized, placebo-controlled study by the ALLG
Authors: Sun Loo, Andrew W. Roberts, Natasha S. Anstee, Glen A. Kennedy, Simon He, Anthony P. Schwarer, Anoop K. Enjeti, James D’Rozario, Paula Marlton, Ian A. Bilmon, John Taper, Gavin Cull, Campbell Tiley, Emma Verner, Uwe Hahn, Devendra K. Hiwase, Harry J. Iland, Nick Murphy, Sundra Ramanathan, John Reynolds, Doen Ming Ong, Ing Soo Tiong, Meaghan Wall, Michael Murray, Tristan Rawling, Joanna Leadbetter, Leesa Rowley, Maya Latimer, Sam Yuen, Stephen B. Ting, Chun Yew Fong, Kirk Morris, Ashish Bajel, John F. Seymour, Mark J. Levis, Andrew H. Wei
Journal: Blood (2023)

Abstract Sorafenib maintenance improves outcomes after hematopoietic cell transplant (HCT) for patients with FMS-like tyrosine kinase 3–internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML). Although promising outcomes have been reported for sorafenib plus intensive chemotherapy, randomized data are limited. This placebo-controlled, phase 2 study (ACTRN12611001112954) randomized 102 patients (aged 18-65 years) 2:1 to sorafenib vs placebo (days 4-10) combined with intensive induction: idarubicin 12 mg/m2 on days 1 to 3 plus either cytarabine 1.5 g/m2 twice daily on days 1, 3, 5, and 7 (18-55 years) or 100 mg/m2 on days 1 to 7 (56-65 years), followed by consolidation and maintenance therapy for 12 months (post-HCT excluded) in newly diagnosed patients with FLT3-ITD AML. Four patients were excluded in a modified intention-to-treat final analysis (3 not commencing therapy and 1 was FLT3-ITD negative). Rates of complete remission (CR)/CR with incomplete hematologic recovery were high in both arms (sorafenib, 78%/9%; placebo, 70%/24%). With 49.1-months median follow-up, the primary end point of event-free survival (EFS) was not improved by sorafenib (2-year EFS 47.9% vs 45.4%; hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.51-1.51; P = .61). Two-year overall survival (OS) was 67% in the sorafenib arm and 58% in the placebo arm (HR, 0.76; 95% CI, 0.42-1.39). For patients who received HCT in first remission, the 2-year OS rates were 84% and 67% in the sorafenib and placebo arms, respectively (HR, 0.45; 95% CI, 0.18-1.12; P = .08). In exploratory analyses, FLT3-ITD measurable residual disease (MRD) negative status (&amp;lt;0.001%) after induction was associated with improved 2-year OS (83% vs 60%; HR, 0.4; 95% CI, 0.17-0.93; P = .028). In conclusion, routine use of pretransplant sorafenib plus chemotherapy in unselected patients with FLT3-ITD AML is not supported by this study.
Peptide delivery of a multivalent mRNA SARS-CoV-2 vaccine
Authors: Cian M. McCrudden, Lindsey Bennie, Philip Chambers, Jordan Wilson, Megan Kerr, Monika Ziminska, Hayley Douglas, Sarah Kuhn, Emma Carroll, Garrett O'Brien, Niamh Buckley, Nicholas J. Dunne, Helen O. McCarthy
Journal: Journal of Controlled Release (2023)

Lipid nanoparticles (LNP) have been instrumental in the success of mRNA vaccines and have opened up the field to a new wave of therapeutics. However, what is ahead beyond the LNP? The approach herein used a nanoparticle containing a blend of Spike, Membrane and Envelope antigens complexed for the first time with the RALA peptide (RALA-SME). The physicochemical characteristics and functionality of RALA-SME were assessed. With >99% encapsulation, RALA-SME was administered via intradermal injection in vivo, and all three antigen-specific IgG antibodies were highly significant. The IgG2a:IgG1 ratio were all >1.2, indicating a robust TH1 response, and this was further confirmed with the T-Cell response in mice. A complete safety panel of markers from mice were all within normal range, supported by safety data in hamsters. Vaccination of Syrian Golden hamsters with RALA-SME derivatives produced functional antibodies capable of neutralising SARS-CoV-2 from both Wuhan-Hu-1 and Omicron BA.1 lineages after two doses. Antibody levels increased over the study period and provided protection from disease-specific weight loss, with inhibition of viral migration down the respiratory tract. This peptide technology enables the flexibility to interchange and add antigens as required, which is essential for the next generation of adaptable mRNA vaccines.
Single-nuclear transcriptome profiling identifies persistent fibroblast activation in hypertrophic and failing human hearts of patients with longstanding disease
Authors: Badder Kattih, Felicitas Boeckling, Mariana Shumliakivska, Lukas Tombor, Tina Rasper, Katja Schmitz, Jedrzej Hoffmann, Luka Nicin, Wesley T Abplanalp, Daniel C Carstens, Mani Arsalan, Fabian Emrich, Tomas Holubec, Thomas Walther, Valentina O Puntmann, Eike Nagel, David John, Andreas M Zeiher, Stefanie Dimmeler
Journal: Cardiovascular Research (2023)

Abstract Aims Cardiac fibrosis drives the progression of heart failure in ischaemic and hypertrophic cardiomyopathy. Therefore, the development of specific anti-fibrotic treatment regimens to counteract cardiac fibrosis is of high clinical relevance. Hence, this study examined the presence of persistent fibroblast activation during longstanding human heart disease at a single-cell resolution to identify putative therapeutic targets to counteract pathological cardiac fibrosis in patients. Methods and results We used single-nuclei RNA sequencing with human tissues from two samples of one healthy donor, and five hypertrophic and two failing hearts. Unsupervised sub-clustering of 7110 nuclei led to the identification of 7 distinct fibroblast clusters. De-convolution of cardiac fibroblast heterogeneity revealed a distinct population of human cardiac fibroblasts with a molecular signature of persistent fibroblast activation and a transcriptional switch towards a pro-fibrotic extra-cellular matrix composition in patients with established cardiac hypertrophy and heart failure. This sub-cluster was characterized by high expression of POSTN, RUNX1, CILP, and a target gene adipocyte enhancer-binding protein 1 (AEBP1) (all P &amp;lt; 0.001). Strikingly, elevated circulating AEBP1 blood level were also detected in a validation cohort of patients with confirmed cardiac fibrosis and hypertrophic cardiomyopathy by cardiac magnetic resonance imaging (P &amp;lt; 0.01). Since endogenous AEBP1 expression was increased in patients with established cardiac hypertrophy and heart failure, we assessed the functional consequence of siRNA-mediated AEBP1 silencing in human cardiac fibroblasts. Indeed, AEBP1 silencing reduced proliferation, migration, and fibroblast contractile capacity and α-SMA gene expression, which is a hallmark of fibroblast activation (all P &amp;lt; 0.05). Mechanistically, the anti-fibrotic effects of AEBP1 silencing were linked to transforming growth factor-beta pathway modulation. Conclusion Together, this study identifies persistent fibroblast activation in patients with longstanding heart disease, which might be detected by circulating AEBP1 and therapeutically modulated by its targeted silencing in human cardiac fibroblasts.